There are presently a number of methods and techniques for the treatment of atherosclerosis among which may be included chemotherapy and surgery. Chemotherapeutic attempts have centered around decreasing serum lipid (cholesterol and triglyceride) levels or altering the metabolism in order to affect the scattered atherosclerotic lesions throughout the body. Surgery is only effective in isolated symptomatic lesions and cannot affect the multitude of atherosclerotic lesions throughout the body.
Theories relating to the etiology of atherosclerosis are many and vary from genetic and ecologic factors to levels of lipids in the bloodstream to injury of the arterial wall.
A safe and effective treatment for atherosclerosis has been the goal of investigators for a substantial period of time. Such a technique, to be successful in the destruction of the arterial lesions must be selective in effect upon the atherosclerotic lesions and produce no irreversible damage to the normal blood vessel. In sum, the treatment of atherosclerosis must selectively differentiate the atherosclerotic portions of the vessel wall from the normal portions of the vessel wall and must selectively destroy the atherosclerotic lesions without affecting the normal vessel.
It has been known that there are certain physical differences that exist between atherosclerotic lesions and a normal blood vessel. One primary physical difference that exists is that atherosclerotic plaques and certain extravascular related lesions (xanthomas, corneal arcus) arise because altered endothelial permeability allows certain macromolecular plasma proteins (which are normally confined to the circulation i.e. lipids) to permeate endothelium and interact with charged components of the connective tissue gel of the vessel wall. The early lesions of atherosclerosis, the fatty streaks and fibrous plaques show evidence of altered permeability in allowing the uptake of protein-bound dyes (trypan blue), colloidal carbon or labeled cholesterol. These substances are taken up by the atherosclerotic lesion but not by the normal blood vessel wall. The normal intima presents a barrier, metabolic or structural, to the influx of serum cholesterol. During atherogenesis this barrier breaks down permitting the entry of blood consituents. This increased permeability has been theorized to be secondary to the release of histamine, kinins, an immunologic reaction or to previous injury or stress. With this increase in permeability there is an uptake of particles normally excluded from the vessel wall.
In addition it has been shown that to a large extent atherosclerotic lesions are monoclonal in nature and result from the overgrowth and excessive proliferation of a single cell line much like a tumor. Profliferation of endothelial and medial smooth muscle cells occurs secondary to trauma or to hyper-chloesterolemia. These proliferating cells take in foreign particles to a high degree.
It is known therefore that the atherosclerotic lesion will take in large amounts of particles secondary to increased permeability. Furthermore the proliferating cells of the atherosclerotic lesion (endothelial and medial smooth muscle cells), phagocytize these particles. The particles are therefore intracellular in these cells of the atherosclerotic lesion as well as being located between the endothelial cell and the internal elastic membrane of the vessel.